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Human immunodeficiency virus type 1 Gag proteins are processed in two cellular compartments
1Department of Medicine, University of North Carolina, Chapel Hill 27599-7295.
Summary
Human immunodeficiency virus type 1 (HIV-1) Gag precursor processing occurs both at the membrane and in the cytoplasm. Cytoplasmic processing, linked to lytic infection, suggests viral protease activity contributing to cell damage.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Retroviral capsid structural proteins are synthesized as Gag polyproteins.
- These Gag precursors are processed by a viral protease for virion formation.
Purpose of the Study:
- To analyze the processing pathway of the human immunodeficiency virus type 1 (HIV-1) Gag precursor (Pr55).
- To investigate the cellular compartments involved in Gag precursor processing and the implications for viral replication and cytotoxicity.
Main Methods:
- Pulse-chase labeling
- Cell fractionation
- Immunoprecipitation
- Treatment with a viral protease inhibitor
Main Results:
- HIV-1 Gag precursor processing occurs via a membrane-associated pathway and also significantly within the cytoplasm.
- Intracellular accumulation of processed viral proteins suggests cytoplasmic protease activity.
- Cytoplasmic processing is associated with lytic HIV-1 infection.
- Protease inhibitor blocked processing in both compartments.
Conclusions:
- The HIV-1 protease is active in the cytoplasmic compartment during lytic infection.
- Cytoplasmic protease activity may lead to cleavage of cellular proteins, contributing to HIV-1-induced cytotoxicity.